ORCID Profile
0000-0001-7534-7154
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UNSW Sydney
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The University of Sydney Sydney University
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The University of Sydney Sydney
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Publisher: Springer Science and Business Media LLC
Date: 09-2020
DOI: 10.1186/S13006-020-00317-5
Abstract: We investigate whether correct infant feeding knowledge and practice differ by maternal HIV status in an era of evolving clinical guidelines in rural South Africa. This cohort study was nested within the MONARCH stepped-wedge cluster-randomised controlled trial ( www.clinicaltrials.gov : NCT02626351 ) which tested the impact of continuous quality improvement on antenatal care quality at seven primary care clinics in KwaZulu-Natal, from July 2015 to January 2017. Women aged ≥18 years at delivery were followed up to 6 weeks postpartum. Clinical data were sourced from routine medical records at delivery. Structured interviews at early postnatal visits and the 6-week postnatal immunisation visit provided data on infant feeding knowledge and feeding practices respectively. We measured the relationship between maternal HIV status and (i) correct infant feeding knowledge at the early postnatal visit and (ii) infant feeding practice at 6 weeks, using Poisson and multinomial regression models, respectively. We analysed data from 1693 women with early postnatal and 471 with 6-week postnatal interviews. HIV prevalence was 47% (95% confidence interval [CI] 42, 52%). Women living with HIV were more knowledgeable than women not living with HIV on correct infant feeding recommendations (adjusted risk ratio, aRR, 1.08, p 0.001). More women living with HIV (33% 95% CI 26, 41%) were not breastfeeding than women not living with HIV (15% 95% CI 11, 21%). However, among women who were currently breastfeeding their infants, fewer women living with HIV (5% 95% CI 2, 9%) mixed fed their babies than women not living with HIV (21% 95% CI 14, 32%). In adjusted analyses, women living with HIV were more likely to avoid breastfeeding (adjusted relative risk ratio, aRRR, 2.78, p 0.001) and less likely to mixed feed (aRRR 0.22, p 0.001) than women not living with HIV. Many mothers in rural South Africa still do not practice exclusive breastfeeding. Women living with HIV were more knowledgeable but had lower overall uptake of breastfeeding, compared with women not living with HIV. Women living with HIV were also more likely to practice exclusive breastfeeding over mixed feeding if currently breastfeeding. Improved approaches are needed to increase awareness of correct infant feeding and exclusive breastfeeding uptake.
Publisher: Oxford University Press (OUP)
Date: 22-10-2012
DOI: 10.1093/CID/CIS919
Publisher: Wiley
Date: 2002
DOI: 10.1046/J.1464-2662.2001.00094.X
Abstract: To estimate the rate of combination antiretroviral treatment change and factors associated with combination antiretroviral treatment change among patients recruited in the Australian HIV Observational Database (AHOD). Analyses were based on patients in the AHOD who had commenced combination antiretroviral treatment after 1 January 1997. Combination antiretroviral treatment change was defined as the addition or change of at least one antiretroviral drug. A random-effect Poisson regression model was used to assess factors associated with increased rates of combination antiretroviral treatment change. A total of 596 patients in the AHOD were included in the analysis, with a median follow-up of 2.3 years. The overall rate of antiretroviral treatment change in this group was 0.45 combinations per year. In a multivariate analysis, a low CD4 count (< 200 cells/microL) at baseline was associated with an increased rate of treatment change [rate ratio (RR)=1.43 95% confidence interval (CI), 1.13, 1.80 P=0.003)]. Combinations including a nonnucleoside reverse transcriptase inhibitor were also associated with slower rates of change than treatment combinations including a protease inhibitor (RR=0.64, 95% CI, 0.51, 0.80, P < 0.001). Initiating combination antiretroviral at a CD4 cell count < 200 cells/microL may be associated with poorer patient outcomes. However, the possibility that clinician or patient concerns about low immunological status led to faster rates of treatment change in this group cannot be discounted.
Publisher: Maad Rayan Publishing Company
Date: 27-10-2020
Abstract: Background: We evaluated continuous quality improvement (CQI) targeting antenatal HIV care quality in rural South Africa using a stepped-wedge cluster-randomised controlled trial (Management and Optimisation of Nutrition, Antenatal, Reproductive, Child health, MONARCH) and an embedded process evaluation. Here, we present results of the process evaluation examining determinants of CQI practice and ‘normalisation.’ Methods: A team of CQI mentors supported public-sector health workers in seven primary care clinics to (1) identify root causes of poor HIV viral load (VL) monitoring among pregnant women living with HIV and repeat HIV testing among pregnant women not living with HIV, and (2) design and iteratively test their own solutions. We used a mixed methods evaluation with field notes from CQI mentors (‘dose’ and ‘reach’ of CQI, causes of poor HIV care testing rates, implemented change ideas) patient medical records (HIV care testing by clinic and time step) and semi-structured interviews with available health workers. We analysed field notes and semi-structured interviews for determinants of CQI implementation and ‘normalisation’ using Normalisation Process Theory (NPT) and Tailored Implementation of Chronic Diseases (TICD) frameworks. Results: All interviewed health workers found the CQI mentors and methodology helpful for quality improvement. Total administered ‘dose’ was higher than planned but ‘reach’ was limited by resource constraints, particularly staffing shortages. Simple workable improvements to identified root causes were implemented, such as a patient tracking notebook and results filing system. VL monitoring improved over time, but not repeat HIV testing. Besides resource constraints, gaps in knowledge of guidelines, lack of leadership, poor clinical documentation, and data quality gaps reduced CQI implementation fidelity and normalisation. Conclusion: While CQI holds promise, we identified several health system challenges. Priorities for policy makers include improving staffing and strategies to improve clinical documentation. Additional support with implementing clinical guidelines and improving routine data quality are needed. Normalising CQI may be challenging without concurrent health system improvements.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2017
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.JHEP.2019.10.010
Abstract: Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2% 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported. In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. clinicaltrials.gov Identifier: NCT03117569. Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%).
Publisher: Wiley
Date: 30-03-2006
DOI: 10.1111/J.1468-1293.2006.00362.X
Abstract: The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) Study, a prospective observational study on a cohort of 23 468 patients with HIV infection, indicated that the incidence of myocardial infarction (MI) increased by 26% per year of exposure to combination antiretroviral treatment (CART). However, it remains unclear whether the observed increase in the rate of MI in this population can be attributed to changes in conventional cardiovascular risk factors. To compare the number of MIs observed among participants in the D:A:D Study with the number predicted by assuming that conventional cardiovascular risk equations apply to patients with HIV infection. The Framingham equation, a conventional cardiovascular risk algorithm, was applied to in idual patient data in the D:A:D Study to predict rates of MI by duration of CART. A series of sensitivity analyses were performed to assess the effect of model and data assumptions. Predictions were extrapolated to provide 10-year risk estimates, and various scenarios were modelled to assess the expected effect of different interventions. In patients receiving CART, the observed numbers of MIs during D:A:D follow up were similar to or somewhat higher than predicted numbers: 9 observed vs 5.5 events predicted, 14 vs 9.8, 22 vs 14.9, 31 vs 23.2 and 47 vs 37.0 for 4 years CART exposure, respectively. In patients who had not received CART, the observed number of MIs was fewer than predicted (3 observed vs 7.6 predicted). Nine per cent of the study population have a predicted 10-year risk of MI above 10%, a level usually associated with initiation of intervention on risk factors. A consistent feature of all analyses was that observed and predicted rates of MI increased in a parallel fashion with increased CART duration, suggesting that the observed increase in risk of MI may at least in part be explained by CART-induced changes in conventional risk factors. These findings provide guidance in terms of choosing lifestyle or therapeutic interventions to decrease those risk factors in much the same way as in persons without HIV infection.
Publisher: Oxford University Press (OUP)
Date: 16-06-2010
DOI: 10.1093/JAC/DKQ231
Abstract: To compare lipid profiles in HIV-infected adults receiving atazanavir-based regimens. We conducted a systematic review of randomized controlled trials (RCTs) comparing atazanavir or atazanavir/ritonavir with a comparator and evaluated lipids at 48 weeks. We searched MEDLINE, EMBASE, CENTRAL, LILACS, Current Controlled Trials, National Institutes of Health Clinical Trials Registry, trials at AIDSinfo and HIV conference proceedings to May 2009. Standardized mean difference (SMD) between study arms in change from baseline to week 48 in lipid parameters was determined weighted by study size and 95% confidence intervals (CI) were calculated. Nine eligible RCTs were identified (n = 3346). SMDs (mmol/L) in four RCTs comparing atazanavir/ritonavir with a ritonavir-boosted protease inhibitor were: total cholesterol, -0.62 (95% CI -0.72, -0.51) low-density lipoprotein (LDL) cholesterol, -0.31 (95% CI -0.44, -0.17) high-density lipoprotein (HDL) cholesterol, -0.16 (95% CI -0.27, -0.06) non-HDL cholesterol, -0.58 (95% CI -0.69, -0.48) and triglycerides, -0.46 (95% CI -0.58, -0.34). Atazanavir compared with non-atazanavir (three RCTs) found lower total, LDL and non-HDL cholesterol, and triglycerides [SMD -0.87 mmol/L (95% CI -0.99, -0.76) -0.56 mmol/L (95% CI -0.67, -0.45) -0.88 mmol/L (95% CI -0.99, -0.76) and -0.56 mmol/L (95% CI -0.75, -0.36), respectively], but HDL cholesterol did not differ [-0.16 mmol/L (95% CI -0.49, 0.16)]. In the atazanavir/ritonavir versus atazanavir comparison (two RCTs), total [SMD 0.44 mmol/L (95% CI 0.23, 0.65)] and non-HDL cholesterol [SMD 0.44 mmol/L (95% CI 0.23, 0.65)] were higher, but HDL cholesterol, LDL cholesterol and triglycerides were not different. At 48 weeks, plasma lipid concentrations were lower with atazanavir/ritonavir than with other ritonavir-boosted protease inhibitor regimens. Total and non-HDL cholesterol were higher with atazanavir/ritonavir than atazanavir alone.
Publisher: Public Library of Science (PLoS)
Date: 08-09-2017
Publisher: Wiley
Date: 04-2007
DOI: 10.1111/J.1468-1293.2007.00448.X
Abstract: Toxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI. We analysed NRTI-sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs. A total of 334 (3.9%) of 8477 patients were included in the present study for a median follow-up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/muL (interquartile range 164-446 cells/muL) and 25% of patients had plasma HIV RNA below 500 HIV-1 RNA copies/mL. In intent-to-treat analysis, 64% of patients had HIV RNA <500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/microL (95% confidence interval 41-76 cells/microL) at 6 months and 111 cells/microL (95% confidence interval 82-140 cells/microL) at 24 months. Prognostic factors for having HIV RNA 2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P-trend=0.002), and those with total cholesterol >6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P-trend <0.001), with an increased risk for patients treated with NNRTI+PIs. Forty-one per cent of patients discontinued their NRTI-sparing regimen. In these antiretroviral-experienced patients, NRTI-sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.
Publisher: Oxford University Press (OUP)
Date: 16-10-2015
DOI: 10.1093/CID/CIU813
Publisher: SAGE Publications
Date: 02-2015
DOI: 10.3851/IMP2774
Abstract: There have been improvements in combination antiretroviral therapy (cART) over the past 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome. Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4 + T-cell count and the proportion of patients with detectable HIV viral load ( copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method. A total of 2,753 patients were included in the analysis: 28% initiated treatment using mono/duo therapy and 72% initiated treatment ≥1996 using cART (30% 1996–1999, 12% 2000–2003, 11% 2004–2007 and 19% ≥2008). Overall CD4 + T-cell count response improved by later era of initiation ( P .001), although 2000–2003 CD4 + T-cell count response was less than that for 1996– 1999 ( P=0.007). The average proportion with detectable viral load from 2 to 4 years post-treatment commencement by era was: mono/duo 0.69 (0.67–0.71), 1996–1999 cART 0.29 (0.28–0.30), 2000–2003 cART 0.22 (0.20–0.24), 2004–2007 cART 0.09 (0.07–0.10) and ≥2008 cART 0.04 (0.03–0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996–1999 to 29% after 2008 ( P .001). Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4 + T-cell count) and also increased durability of first-line ART regimens.
Publisher: Mary Ann Liebert Inc
Date: 12-2021
Publisher: Wiley
Date: 05-2005
DOI: 10.1111/J.1468-1293.2005.00280.X
Abstract: To assess the impact of highly active antiretroviral therapy (HAART) on rates of change of antiretroviral treatment among patients co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in the Australian HIV Observational Database (AHOD). Analysis was based on 805 of the 2218 patients recruited to the AHOD by March 2003, who had commenced HAART after 1 January 1997, who had recorded test results for HBV surface antigen and anti-HCV antibody, and who had follow-up of more than 3 months. The effect of hepatitis co-infection on the rate of antiretroviral treatment change after commencing HAART was assessed using a random-effect Poisson regression model. Among those included in the analyses, the prevalences of HBV and HCV were 4.8% and 12.8%, respectively. The overall rate of combination antiretroviral treatment change was 0.74 combinations per year. Factors independently associated with an increased rate of change of combination antiretroviral treatment were: prior AIDS-defining illness prior exposure to double combination antiretroviral therapy and antiretroviral treatment class. Co-infection with HBV and/or HCV was not found to be significantly associated with the rate of combination antiretroviral treatment change. While both HBV and HCV co-infections are relatively common in the AHOD, they do not appear to be serious impediments to the treatment of HIV-infected patients.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-05-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: The American Association of Immunologists
Date: 2011
Abstract: The CTL response in HLA-B*27+ HIV-infected in iduals is characterized by an immunodominant response to a conserved epitope in gag p24 (aa 263–272, KRWIILGLNK KK10). Mutations resulting in substitution of the arginine (R264) at position 2 of this epitope have been identified as escape mutations. Nineteen HLA-B*27+ long-term nonprogressors were identified from an Australian cohort with an average follow-up of 16 y following infection. Viral and host genetic factors impacting on disease progression were determined at multiple time points. Twelve of 19 had wild-type sequences at codon 264 at all time points 7 of 19 carried CTL escape variants. Median viral load and CD4+ T cell counts were not significantly different between these groups at enrollment. Viral load, as judged by levels at their last visit (1,700 and 21,000 RNA copies/ml, respectively p = 0.01) or by time-weighted area under the curve was higher in the escape group (p = 0.02). Escape mutants at other HLA-B*27–restricted epitopes were uncommon. Moreover, host polymorphisms, such as CCR5Δ32, CCR2-64I, and SDF1-3′A, or breadth of TCR repertoire responding to KK10 did not segregate to wild-type or escape groups. Host and viral factors were examined for a relationship to viral load. The only factor to affect viral load was the presence of the R264 escape mutations at the immunodominant epitope. CTL escape at R264 in the KK10 epitope is a major determinant of subsequent viral load in these HLA-B*27+ in iduals.
Publisher: Public Library of Science (PLoS)
Date: 27-02-2015
Publisher: Wiley
Date: 12-2018
DOI: 10.1111/IMJ.14040
Publisher: Cold Spring Harbor Laboratory
Date: 22-11-2020
DOI: 10.1101/2020.11.19.20235069
Abstract: People with HIV have higher rates of certain comorbidities, particularly cardiovascular disease and some malignancies, than people without HIV. As somatic mutations associated with age-related clonal haematopoiesis (CH) are linked to similar comorbidities in the general population, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study recruiting 220 HIV-positive and 226 HIV-negative participants aged 55 years or older in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess for the presence of CH mutations and identify potential risk factors for and clinical sequelae of CH. Investigators testing for CH were blinded to participants’ HIV status. In total, 132 CH mutations were identified in 99 (22.2%) of 446 participants. CH was more prevalent in HIV-positive participants than HIV-negative participants (27.7% vs. 16.8%, p =0.006), overall and across all age groups. HIV infection was associated with an increased odds of having CH (adjusted odds ratio 2.10, 95% confidence interval 1.30-3.38, p=0.002). The most common genes mutated were DNMT3A (48.5%), TET2 (20.5%) and ASXL1 (11.4%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-04-2021
Publisher: MDPI AG
Date: 31-07-2020
DOI: 10.3390/MICROORGANISMS8081164
Abstract: Background: the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases. Methods: RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12. Results: Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40–56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8–17.6), with 89.5% having a VL & copies/mL and the median CD4 count being 621 cells/µL (438–830). Malignancies (n = 361) and cardiovascular disease (n = 168) were the predominant reported clinical events. Conclusion: RESPOND’s large, erse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the erse modern challenges for PLWH.
Publisher: Wiley
Date: 18-02-2019
DOI: 10.5694/MJA2.50006
Abstract: To determine trends in and predictors of early treatment for people newly diagnosed with human immunodeficiency virus (HIV) infection in Australia. Retrospective cohort analysis of routinely collected longitudinal data from 44 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) program. Patients diagnosed with HIV infections, January 2004 - June 2015. Commencement of antiretroviral therapy within 6 months of HIV diagnosis (early treatment) demographic, clinical, and risk group characteristics of patients associated with early treatment trends in early treatment, by CD4 917 people were diagnosed with HIV infections, their median age was 34 years (interquartile range [IQR]: 27-43 years), and 841 (92%) were men the median CD4 The proportion of people newly diagnosed with HIV in sexual health clinics in Australia who received treatment within 6 months of diagnosis increased from 17% to 53% during 2004-2015, reflecting changes in the CD4
Publisher: Elsevier BV
Date: 05-2012
Publisher: Public Library of Science (PLoS)
Date: 31-03-2015
Publisher: Wiley
Date: 22-02-2017
DOI: 10.1111/HIV.12504
Publisher: Elsevier BV
Date: 08-2018
Publisher: Springer Science and Business Media LLC
Date: 04-10-2018
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/SH11020
Abstract: In the developed world, HIV infection is now well managed with very effective and less toxic antiretroviral treatment. HIV-positive patients therefore are living longer, but are now faced by challenges associated with aging. Several non-AIDS associated morbidities are increased in this population, including cardiovascular disease (CVD). It is suggested that CVD occurs earlier among HIV-positive patients compared with HIV-negative patients, and at a higher rate. Several factors have been proposed to contribute to this. First, the traditional CVD risk factors are highly prevalent in this population. High rates of smoking, dyslipidaemia and a family history of CVD have been reported. This population is also aging, with estimates of more than 25% of HIV-positive patients in the developed world being over the age of 50. Antiretroviral treatment, both through its effect on lipids and through other, sometimes less well understood, mechanisms, has been linked to increased CVD risk. HIV infection, especially untreated, is a further contributing factor to increased CVD risk in HIV-positive patients. As the HIV-positive population continues to age, the risk of CVD will continue to increase. Guidelines for the management and prevention of CVD risk have been developed, and are largely modelled on those used in the general population. However, the data currently suggest that these interventions, such as the use of lipid-lowering medications and smoking cessation programs, remain quite low. A better understanding the mechanisms of CVD risk in this aging population and further efforts in improving uptake of prevention strategies will remain an important research area.
Publisher: American College of Physicians
Date: 06-2021
DOI: 10.7326/M20-5226
Publisher: Wiley
Date: 03-2022
DOI: 10.1111/HIV.13273
Abstract: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)‐based antiretroviral therapy (ART) versus non‐nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. Eligible people with HIV were aged ≥18 years who initiated a new three‐drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow‐up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113–130) mmHg, 78 (70–82) mmHg, and 43 (34–50) years, respectively. Over 8380.4 person‐years (median follow‐up 1.5 [IQR 1.0–2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person‐years, 95% confidence interval [CI] 118.9–134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76 95% CI 1.47–2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07 95% CI 0.89–1.29). The results were similar when the analysis was stratified by ART status at baseline. Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART‐naïve and ART‐experienced participants within RESPOND.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.JHEP.2021.04.056
Abstract: Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens however, large randomised studies are lacking. REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. The primary analysis population consisted of 188 randomised participants at termination of study enrolment short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7 difference -8.3%, p = 0.025). In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS. NCT02625909.
Publisher: Public Library of Science (PLoS)
Date: 19-02-2014
Publisher: JMIR Publications Inc.
Date: 29-06-2022
Abstract: ustralia has set the goal for the virtual elimination of HIV transmission by the end of 2022, yet accurate information is lacking on the level of HIV transmission occurring among residents. We developed a method for estimating the timing of HIV acquisition among migrants, relative to their arrival in Australia, and applied it to surveillance data from the Australian National HIV Registry. To apply a novel algorithm to ascertain the level of HIV transmission occurring among migrants before and after migration, and to inform appropriate local public health interventions. o apply a novel algorithm to ascertain the level of HIV transmission occurring among migrants before and after arrival in Australia, and to inform appropriate local public health interventions.We developed an algorithm incorporating CD4+ T-cell decline back-projection and enhanced variables (clinical presentation, past HIV testing history and clinician estimate of the place of HIV acquisition) and compared it to a standard algorithm which uses CD4+ T-cell back-projection only. We applied both of these algorithms to all new HIV diagnoses among migrants to estimate whether HIV infection occurred before or after arrival in Australia. e developed an algorithm incorporating CD4+ T-cell decline back-projection and enhanced variables (clinical presentation, past HIV testing history and clinician estimate of the place of HIV acquisition) and compared it to a standard algorithm which uses CD4+ T-cell back-projection only. We applied both of these algorithms to all new HIV diagnoses among migrants to estimate whether HIV infection occurred before or after arrival in Australia. etween 1 January 2016 and 31 December 2020, 1,909 migrants were newly diagnosed with HIV in Australia, 85% were men, and the median age was 33 years. Using the enhanced algorithm, 923 (48%) were estimated to have acquired HIV after arrival in Australia, 640 (34%) before arrival (from overseas), 248 (13%) close to arrival, and 98 (5%) were unable to be classified. Using the standard algorithm, 610 (32%) were estimated to have acquired HIV in Australia, 483 (25%) before arrival, 322 (17%) close to arrival, and 494 (26%) were unable to be classified. sing our algorithm, close to half of migrants diagnosed with HIV were estimated to have acquired HIV after arrival in Australia, highlighting the need for tailored culturally appropriate testing and prevention programs to limit HIV transmission and achieve elimination targets. Our method reduced the proportion of HIV cases unable to be classified and can be adopted in other countries with similar HIV surveillance protocols, to inform epidemiology and elimination efforts.
Publisher: Wiley
Date: 18-11-2015
DOI: 10.1111/HIV.12188
Publisher: Wiley
Date: 06-2023
DOI: 10.1002/JIA2.26127
Abstract: Australia has set the goal for the virtual elimination of HIV transmission by the end of 2022, yet accurate information is lacking on the level of HIV transmission occurring among residents. We developed a method for estimating the timing of HIV acquisition among migrants, relative to their arrival in Australia. We then applied this method to surveillance data from the Australian National HIV Registry with the aim of ascertaining the level of HIV transmission among migrants to Australia occurring before and after migration, and to inform appropriate local public health interventions. We developed an algorithm incorporating CD4 + T‐cell decline back‐projection and enhanced variables (clinical presentation, past HIV testing history and clinician estimate of the place of HIV acquisition) and compared it to a standard algorithm which uses CD4 + T‐cell back‐projection only. We applied both algorithms to all new HIV diagnoses among migrants to estimate whether HIV infection occurred before or after arrival in Australia. Between 1 January 2016 and 31 December 2020, 1909 migrants were newly diagnosed with HIV in Australia, 85% were men, and the median age was 33 years. Using the enhanced algorithm, 932 (49%) were estimated to have acquired HIV after arrival in Australia, 629 (33%) before arrival (from overseas), 250 (13%) close to arrival and 98 (5%) were unable to be classified. Using the standard algorithm, 622 (33%) were estimated to have acquired HIV in Australia, 472 (25%) before arrival, 321 (17%) close to arrival and 494 (26%) were unable to be classified. Using our algorithm, close to half of migrants diagnosed with HIV were estimated to have acquired HIV after arrival in Australia, highlighting the need for tailored culturally appropriate testing and prevention programmes to limit HIV transmission and achieve elimination targets. Our method reduced the proportion of HIV cases unable to be classified and can be adopted in other countries with similar HIV surveillance protocols, to inform epidemiology and elimination efforts.
Publisher: SAGE Publications
Date: 10-2011
DOI: 10.3851/IMP1906
Abstract: We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA ,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS ≥4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS 2.5–3.5 and ≥4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Median (IQR) age was 38 (34–42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8–4.5) years. Median (IQR) CD4 + T-cell count and HIV RNA were 194 (121–280) cells/mm 3 and 4.1 (3.6–4.6) log 10 copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5–3.5 and ≥4, respectively. Only HIV RNA≥4 log 10 copies/ml at failure was associated with both Monogram WS≥4 (OR 2.3, 95% CI 1.3–3.9 P=0.003) and DUET WS≥2.5 (OR 1.9, 95% CI 1.1–3.3 P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.
Publisher: Oxford University Press (OUP)
Date: 15-03-2004
DOI: 10.1086/381783
Publisher: American Association for Cancer Research (AACR)
Date: 30-06-2016
DOI: 10.1158/1055-9965.EPI-15-1106
Abstract: Background: There is debate about the accuracy of anal cytology and high-resolution anoscopy (HRA), in the diagnosis of anal human papillomavirus (HPV)-related squamous intraepithelial lesions (SIL). Few studies have performed both simultaneously in a large s le of high-risk in iduals. Methods: At baseline in a community-based cohort of HIV-infected and uninfected homosexual men ages ≥35 years in Sydney, Australia, all men underwent anal swabbing for cytology and HPV genotyping, and HRA-guided biopsy. We evaluated the separate and combined diagnostic accuracy of cytology and histology, based on a comparison with the prevalence of HPV16 and other high-risk (HR) HPV. We examined trends in HPV prevalence across cytology–histology combinations. Results: Anal swab, HRA, and HPV genotyping results were available for 605 of 617 participants. The prevalence of cytologically predicted high-grade SIL (HSIL, 17.9%) was lower than histologically diagnosed HSIL (31.7%, P & 0.001). The prevalence of composite-HSIL (detected by either method) was 37.7%. HPV16 prevalence was similar in men with HSIL by cytology (59.3%), HSIL by histology (51.0%), and composite-HSIL (50.0%). HPV16 prevalence was 31.1% in men with composite-atypical squamous cells suggestive of HSIL, to 18.5% in men with composite-low-grade SIL, to 12.1% in men with composite-negative results (Ptrend & 0.001). Conclusions: Significantly more HSIL was detected when a composite cytology–histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence. Impact: These data suggest that a composite cytology–histology endpoint reflects meaningful disease categories and is likely to be an important biomarker in anal cancer prevention. Cancer Epidemiol Biomarkers Prev 25(7) 1134–43. ©2016 AACR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
Publisher: Public Library of Science (PLoS)
Date: 16-08-2010
Publisher: Springer Science and Business Media LLC
Date: 25-03-2014
Publisher: Wiley
Date: 2010
Abstract: This retrospective survey describes types of cancers diagnosed in HIV‐infected subjects in Asia, and assesses risk factors for cancer in HIV‐infected subjects using contemporaneous HIV‐infected controls without cancer. TREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV‐related information. For risk factor analyses, two HIV‐infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS‐defining cancers (ADCs), and non‐ADCs. Non‐ADCs were further categorized as being infection related (NADC‐IR) and unrelated (NADC‐IUR). A total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%). The mean age (SD) for cases was 39 (10.6), 46 (11.5) and 44 (13.7) for ADCs, NADC‐IURs and NADCs‐IR, respectively. The majority (66%) of cancers were ADCs (16% Kaposi sarcoma, 40% non‐Hodgkin's lymphoma, and 9% cervical cancer). The most common NADCs were lung (6%), breast (5%) and hepatocellular carcinoma and Hodgkin's lymphoma (2% each). There were also three (1.4%) cases of leiomyosarcoma reported in this study. In multivariate analyses, in iduals with CD4 counts above 200 cells/mm 3 were approximately 80% less likely to be diagnosed with an ADC (p 0.001). Older age (OR: 1.39, p = 0.001) and currently not receiving antiretroviral treatment (OR: 0.29, p = 0.006) were independent predictors of NADCs overall, and similarly for NADCs‐IUR. Lower CD4 cell count and higher CDC stage (p = 0.041) were the only independent predictors of NADCs‐IR. The spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non‐Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smooth‐muscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-12-2016
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.VACCINE.2011.01.114
Abstract: HIV infected in iduals have poorer response to hepatitis B vaccine (HBV) compared to normal host. Intradermal administration (i.d.) facilitates the exposure of antigen to antigen-presenting cells compared to intramuscular administration (i.m.). HIV-infected children aged 1-18 years with CD4%≥15% or 200 cells/mm(3) who had negative HBs Ag, antiHBs, and antiHBc were randomized to receive 3-dose of HBV via i.d. (2 μg/dose) or i.m. (10 μg/dose) route at months 0, 2, and 6. AntiHBs titers were measured at months 2, 6 and 7 after first HBV. AntiHBs≥10 mIU/mL was considered protective and AntiHBs>100 mIU/mL was considered good response. Participants included 41 in i.d. and 39 in i.m. arms. 64% had completed 3-doses HBV during infancy. The mean (SD) of age, nadir CD4% and current CD4% were 12 (3.3) years, 10.6 (7.9)% and 28 (8.0)% respectively. 91% were on HAART and 84% had undetectable HIV-RNA. Proportion of children with protective antiHBs in i.d. vs. i.m. group were 19.5% vs. 25.6% at month 2, 56.1% vs. 76.9% at month 6, and 90.2% vs. 92.3% at month 7 (NS, all). The geometric mean (95% confidence interval) of antiHBs titer in i.d. vs. i.m. group were 112.5 (34.4-367.6) vs. 141.2 (49.4-404.1) mIU/mL at month 2 (p=0.74), 70.4 (39.8-124.4) vs. 132.1 (79.4-219.8) mIU/mL at month 6 (p=0.10), and 157.0 (103.0-239.3) vs. 458.9 (324.0-647.0) mIU/mL at month 7 (p<0.001). However, only 56.1% of the i.d. arm had good response to HBV compared to 82.1% in the i.m. arm (p=0.01). The predictors for being a good responder to HBV were i.m. administration [OR 4.0, 95%CI 1.4-11.8, p=0.012] and body weight <35 kg at baseline [OR 3.8, 95%CI 1.3-10.8, p=0.013]. No adverse events grade 3/4 occurred. In conclusion, HIV-infected children without severe immune suppression, both i.d. and i.m. routes of HBV resulted in similar rates of protective antibody titers. However, high antibody titers to HBV were more common with i.m. therefore, i.m. administration is preferred.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.CANEP.2018.10.009
Abstract: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. Among 414 MSM included (composite-HSIL (n = 231) negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014 anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057 anal lump within last 6 months: p = 0.182). Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.
Publisher: Wiley
Date: 20-01-2011
Publisher: Wiley
Date: 28-03-2016
DOI: 10.1111/HIV.12371
Publisher: Elsevier BV
Date: 10-2021
Publisher: SAGE Publications
Date: 20-04-2011
Abstract: The significance of interethnic variation in CD4 counts between Asian and Caucasian populations is not known. Patients on combination antiretroviral therapy from Treat Asia and Australian HIV Observational Databases (TAHOD, predominantly Asian, n = 3356 and AHOD, predominantly Caucasian, n = 2312, respectively) were followed for 23 144 person-years for AIDS/death and all-cause mortality endpoints. We calculated incidence-rates and used adjusted Cox regression to test for the interaction between cohort (TAHOD/AHOD) and time-updated CD4 count category (lagged by 3 months) for each of the endpoints. There were 382 AIDS/death events in TAHOD (rate: 4.06, 95%CI: 3.68-4.50) and 305 in AHOD (rate: 2.39, 95%CI: 2.13-2.67), per 100 person-years. At any given CD4 count category, the incidence-rates of endpoints were found to be similar between TAHOD and AHOD (in the adjusted models, P .05 for the interaction term between cohort type and latest CD4 counts). At any given CD4 count, risk of AIDS or death was not found to vary by ethnicity, suggesting that the CD4 count thresholds for predicting outcomes defined in Caucasian populations may be equally valid in Asian populations.
Publisher: Wiley
Date: 10-11-2010
Publisher: CSIRO Publishing
Date: 2008
DOI: 10.1071/SH07082
Abstract: Objectives: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. Methods: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of in iduals on ART and the proportion of in iduals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. Results: We estimated that the numbers of in iduals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of in iduals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81–92%) and two large, community-based surveys in Australia (69–85% and 49–83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria however, the s le size was very small. Conclusions: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of in iduals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.
Publisher: Wiley
Date: 04-10-2013
Publisher: SAGE Publications
Date: 02-2015
DOI: 10.3851/IMP2822
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.DRUGPO.2018.10.004
Abstract: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST. D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12). Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1 non-adherence, n = 1 incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1 death, n = 1 virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly robably related to therapy nausea and myoclonus). Two cases of reinfection were observed. Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST.
Publisher: Wiley
Date: 30-08-2013
Publisher: Oxford University Press (OUP)
Date: 09-04-2022
DOI: 10.1093/CID/CIAC249
Abstract: Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500–599, 600–799, or ≥ 800 cells/mm3. After 36–44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. We enrolled 146 PWH, 36 in the 500–599, 60 in the 600–799, and 50 in the ≥ 800 CD4 strata. After 36–44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600–799 or 500–599 cells/mm3. The median level of HIV-DNA after 36–44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500–599 cells/mm3 (median [interquartile range]: 16.3 [7.0–117.6] vs 68.4 [13.7–213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600–799 or 500–599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.
Publisher: Oxford University Press (OUP)
Date: 23-12-2020
DOI: 10.1093/CID/CIAA1878
Abstract: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. Antiretroviral treatment–experienced in iduals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012–1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. Of 9791 in iduals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%) the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). In iduals on 2DRs were older (median, 52.6 years [interquartile range, 46.7–59.0] vs 47.7 [39.7–54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU 95% confidence interval [CI]: 20.7–24.5) on 3DRs and 79 (30.9/1000 PYFU 95% CI: 24.8–38.5) on 2DRs. The most common events were death (7.5/1000 PYFU 95% CI: 6.5–8.6) and non-AIDS cancer (5.8/1000 PYFU 95% CI: 4.9–6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92 95% CI: .72–1.19 P = .53). This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.
Publisher: Wiley
Date: 2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-05-2013
DOI: 10.1002/HEP.26263
Publisher: BMJ
Date: 06-01-2020
Publisher: Massachusetts Medical Society
Date: 26-04-2007
DOI: 10.1056/NEJMOA062744
Publisher: Wiley
Date: 26-06-2020
DOI: 10.1111/HIV.12888
Abstract: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real‐world settings are limited. The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL 200 HIV‐1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count 750 cells/μL or a 33% increase where the baseline CD4 count was ≥ 500 cells/μL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. Of 5198 ART‐naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs 880 (17.4%) were aged 50 years, 2539 (49.4%) had CD4 counts 350 cells/μL and 1891 (36.8%) had VL 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40–50 and 50 years), CD4 count categories (≤ 350 vs. 350 cells/μL) and VL categories at ART initiation (≤ 100 000 vs. 100 000 copies/mL), with all investigated interactions being nonsignificant ( P 0.05). Differences among ART classes in virological, immunological and clinical outcomes in ART‐naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/SH15124
Abstract: Background Gender differences vary across geographical settings and are poorly reported in the literature. The aim of this study was to evaluate demographics and clinical characteristics of participants from the Australian HIV Observational Database (AHOD), and to explore any differences between females and males in the rate of new clinical outcomes, as well as initial immunological and virological response to antiretroviral therapy. Methods: Time to a new clinical end-point, all-cause mortality and/or AIDS illness was analysed using standard survival methods. Univariate and covariate adjusted Cox proportional hazard models were used to evaluate the time to plasma viral load suppression in all patients that initiated antiretroviral therapy (ART) and time to switching from a first-line ART to a second-line ART regimen. Results: There was no significant difference between females and males for the hazard of all-cause mortality [adjusted hazard ratio: 0.98 (0.51, 1.55), P = 0.67], new AIDS illness [adjusted hazard ratio: 0.75 (0.38, 1.48), P = 0.41] or a composite end-point [adjusted hazard ratio: 0.74 (0.45, 1.21), P = 0.23]. Incident rates of all-cause mortality were similar between females and males 1.14 (0.61, 1.95) vs 1.28 (1.12, 1.45) per 100 person years. Virological response to ART was similar for females and males when measured as time to viral suppression and/or time to virological failure. Conclusion: This study supports current Australian HIV clinical care as providing equivalent standards of care for male and female HIV-positive patients. Future studies should compare ART-associated toxicity differences between ART-associated toxicity differences between men and women living with HIV in Australia.
Publisher: Elsevier BV
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 06-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-10-2016
DOI: 10.1002/HEP.28844
Abstract: While interferon‐based therapy has excellent efficacy in acute and recent hepatitis C virus (HCV) infection, the side effect profile limits implementation. Sofosbuvir and ribavirin for 12‐24 weeks is safe and well tolerated in chronic HCV, with efficacy dependent on genotype and disease stage. The aim of this study was to assess the efficacy of sofosbuvir and ribavirin for 6 weeks in in iduals with recent HCV infection. In this open‐label study conducted in Australia and New Zealand, adults with recent HCV (duration of infection months) received sofosbuvir 400 mg daily and weight‐based ribavirin ( kg, 1,000 mg/day ≥75 kg, 1,200 mg/day) for 6 weeks. The primary efficacy endpoint was sustained virological response at posttreatment week 12 (SVR12). Nineteen participants commenced sofosbuvir and ribavirin (89% male, 74% with human immunodeficiency virus, 68% genotype 1a). Four (21%) reported a symptomatic HCV seroconversion illness, including 2 with jaundice. At baseline, median HCV RNA was 5.4 log 10 IU/mL (interquartile range 4.4‐6.8) and median estimated duration of infection was 37 weeks (interquartile range 27‐41). At the end of treatment, HCV RNA was nonquantifiable in 89% (n = 17). SVR4 and SVR12 were 42% (n = 8) and 32% (n = 6), respectively. Treatment failure was due to nonresponse (n = 2), posttreatment relapse (n = 9), reinfection (n = 1), and loss to follow‐up (n = 1). The regimen was well tolerated with minimal hematological toxicity. SVR12 was related to baseline HCV RNA (≤6 log 10 IU/mL, P = 0.018) and early on‐treatment viral kinetics (HCV RNA below the level of quantitation at week 1, P = 0.003). Conclusion : Six weeks of sofosbuvir and ribavirin was safe and well tolerated, but efficacy was suboptimal further research is needed to determine whether more potent interferon‐free direct‐acting antiviral regimens will allow treatment duration to be shortened in recent, predominantly asymptomatic HCV infection. (H epatology 2016 :1911‐1921).
Publisher: Oxford University Press (OUP)
Date: 04-02-2021
DOI: 10.1093/AJE/KWAB014
Abstract: Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 07-2010
Publisher: Wiley
Date: 05-2005
DOI: 10.1111/J.1468-1293.2005.00292.X
Abstract: HIV disease progression has been well documented in Western populations. This study aimed to estimate the short-term risk of AIDS and death from the TREAT Asia HIV Observational Database (TAHOD), a prospective, multicentre cohort study in Asia and the Pacific region. Prospective data were analysed to estimate short-term disease progression. Endpoints were defined as the time from study entry to diagnosis with AIDS or death. Antiretroviral treatment was fitted as a time-dependent variable. Predictors of disease progression were assessed using Cox proportional hazards models, and prognostic models were developed using Weibull models. A total of 1260 patients with prospective follow-up data contributed 477 person-years of follow-up, during which 18 patients died and 34 were diagnosed with AIDS, a combined rate of 10.1 per 100 person-years. Compared with patients receiving antiretroviral treatment, patients not on treatment had a higher rate of disease progression (17.6 vs. 8.1 per 100 person-years, respectively). Baseline CD4 count was the strongest predictor of disease progression. Prognostic models, using either a baseline CD4 count as the sole marker or markers including baseline haemoglobin, AIDS-related symptoms and previous or current antiretroviral treatment, were successful at identifying patients at high risk of short-term disease progression. Similar to the situation in Western countries, baseline CD4 count was the strongest predictor of short-term disease progression. Prognostic models based on readily available clinical data and haemoglobin level should be useful in estimating short-term clinical risk in HIV-infected patients in Asia and the Pacific region.
Publisher: SAGE Publications
Date: 07-2016
DOI: 10.3851/IMP3073
Publisher: Oxford University Press (OUP)
Date: 10-2010
DOI: 10.1086/656363
Abstract: Antiretroviral therapy is complicated by drug interactions and contraindications. Novel regimens are needed. This open label study randomly assigned treatment-naive, human immunodeficiency virus (HIV)-infected subjects to receive tenofovir-emtricitabine with efavirenz (Arm I), with ritonavir-boosted atazanavir (Arm II), or with zidovudine/abacavir (Arm III). Pair-wise comparisons of differences in time-weighted mean change from baseline plasma HIV-RNA to week 48 formed the primary analysis. Treatment arms were noninferior if the upper limit of the 95% confidence interval (CI) was <0.5 log(10) copies/mL. Secondary objectives included virologic, immunologic and safety end points. The intention-to-treat population comprised 322 patients (Arm I, n = 114 Arm II, n = 105 and Arm III, n = 103). Noninferiority for the primary end point was established. Analysis for superiority showed that Arm III was significantly less potent than Arm I (-0.20 log(10) copies/mL 95% CI, -0.39 to -0.01 log(10) copies/mL P = .038). The proportions of patients on each of Arm I (95%) and Arm II (96%) with <200 copies/mL were not different (P = .75), but the percentage of patients in Arm III with <200 copies/mL (82%) was significantly lower (P = .005). CD4+ cell counts did not differ. Serious adverse events were more frequent in Arm III (n = 30) than in Arm I or Arm II (n = 15 for each P = .062). A novel quadruple nucleo(t)side combination demonstrated significantly less suppression of HIV replication, compared with the suppression demonstrated by standard antiretroviral therapy regimens, although it did meet the predetermined formal definition of noninferiority. Secondary analyses indicated statistically inferior virologic and safety performance. Efavirenz and ritonavir-boosted atazanavir arms were equivalent in viral suppression and safety.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-12-2007
DOI: 10.1097/QAI.0B013E318158BEC9
Abstract: Facial lipoatrophy can stigmatize and can reduce quality of life, self esteem, and antiretroviral adherence. Poly-L-lactic acid (PLA) injections seem safe and effective, but no randomized study has included objective endpoints. HIV-positive adults with moderate/severe facial lipoatrophy were randomized to 4 open-label PLA treatments administered every 2 weeks from week 0 (immediate group, n = 51) or after week 24 (deferred group, n = 50). The primary endpoint was mean change in facial soft tissue volume (FSTV), as assessed by spiral computed tomography. Analyses were by intention to treat. At week 24, mean changes in FSTV were 0 cm3 in the intermediate group and -10 cm3 in the deferred group (between-group difference of 10 [95% confidence interval (CI): -7 to 28] cm3 P = 0.24). The immediate group had a greater mean change in soft tissue depth at the maxilla (2.2 mm [95% CI: 1.6 to 2.9] P < 0.0001) and base of the nasal septum (1.0 mm [95% CI: 0.3 to 1.6] P = 0.003) levels. PLA did not have an impact on peripheral fat mass, viral load, or antiretroviral adherence. Patient and physician subjectively assessed facial lipoatrophy severity (P < 0.0001), 2 of 8 Short Form-36 Health Survey and 2 of 5 Multidimensional Body-Self Relations Questionnaire-Appearance Scales, scores improved significantly. The median duration of treatment-related adverse events was 2 (interquartile range: 1 to 3) days. PLA did not increase FSTV, although tissue thickness in injection planes increased modestly, an improvement observed by patients. PLA was safe and well tolerated. Facial lipoatrophy severity and some quality-of-life domains improved.
Publisher: Elsevier BV
Date: 02-2003
DOI: 10.1016/S1386-6532(02)00119-1
Abstract: To illustrate how human immunodeficiency virus (HIV) observational databases may be used to monitor trends in HIV treatment and HIV disease outcomes through data reported from the Australian HIV Observational Database (AHOD). Time trends in the use of antiretroviral treatment, and changes in treatment strategies were calculated in patients recruited to AHOD from HIV specialist clinics including hospitals, sexual health clinics and general practices. These results were then compared to trends reported from other observational cohorts. By September 2001, 1961 patients were recruited to AHOD. Since entering AHOD, 3% of patients have been diagnosed with an AIDS defining illness, and 2% of patients have died, of which, 54% were non-HIV related deaths. The proportion of patients receiving antiretroviral therapy increased from 66% between January and June 1998 and 77% between July and September 2001. The most commonly received treatment regimen was triple therapy including a protease inhibitor (PI), ranging between 36% in January and June 1998 and 31% in July to September 2001. Triple therapy including a non-nucleoside reverse transcriptase inhibitor (NNRTI) more than doubled to 32% between July and September 2001. The proportion of patients receiving either stavudine (d4T) or zidovudine (AZT) treatment regimens decreased from 92% between January and June 1998 to 76% between July and September 2001. Patients receiving ritonavir in combination with another PI increased, as did the proportion of patients interrupting therapy for more than 3 months. These findings suggest there have been changes in the way antiretroviral treatments have been used in Australia, and are consistent with the current literature. Furthermore, these findings demonstrate the usefulness of observational cohorts as a surveillance tool monitoring trends in treatment and disease progression.
Publisher: Elsevier BV
Date: 07-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-01-2021
Publisher: Oxford University PressOxford
Date: 28-08-2008
DOI: 10.1093/ACPROF:OSO/9780199225859.003.0006
Abstract: This chapter discusses HIV in Australia. Topics covered include epidemiology of HIV infection in Australia, primary and newly diagnosed HIV infection in Australia, treatment strategies during the era of HAART in Australia, and the impact of HAART in Australia.
Publisher: Wiley
Date: 08-05-2018
DOI: 10.1111/JVH.12917
Abstract: Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection 10 x ULN was documented in 83% (n = 25) one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log
Publisher: CSIRO Publishing
Date: 2006
DOI: 10.1071/SH05045
Abstract: Introduction: Mortality rates in HIV-infected people remain high in the era of highly active antiretroviral treatment (HAART). The objective of this paper was to examine causes of deaths in the Australian HIV Observational Database (AHOD) and compare risk factors for HIV-related and HIV-unrelated deaths. Methods: Data from AHOD, an observational study of people with HIV attending medical sites between 1999 and 2004, were analysed. Primary and underlying causes of death were ascertained by sites completing a standardised cause of death form. Causes of death were then coded as HIV-related or HIV-unrelated. Risk factors for HIV-related and unrelated deaths were assessed using survival analysis among patients who had a baseline and at least one follow-up CD4 and RNA measure. Results: The AHOD had enrolled 2329 patients between 1999 and 2004. During this time, a total of 105 patients died, with a crude mortality rate of 1.58 per 100 person years. Forty-two (40%) deaths were HIV-related (directly attributable to an AIDS event), 55 (52%) HIV-unrelated (all other causes), and eight had unknown cause of death. Independent risk factors for HIV-related deaths were low CD4 count and receipt of a larger number of antiretroviral treatment combinations. Among HIV-unrelated deaths, low CD4 count and older age were independent risk factors. Conclusions: In AHOD in the HAART era, mortality in people with HIV remains around 10-fold higher than in the general population. In our analyses, HIV-unrelated deaths were associated with more advanced HIV disease in a similar way to HIV-related deaths.
Publisher: CSIRO Publishing
Date: 2014
DOI: 10.1071/SH13074
Abstract: Background In HIV-positive people, sexually transmissible infections (STIs) probably increase the infectiousness of HIV. Methods: In 2010, we established a cohort of in iduals (n = 554) from clinics in the Australian HIV Observational Database (AHOD). We calculated retrospective rates for four STIs for 2005–10 and prospective incidence rates for 2010–11. Results: At baseline (2010), patient characteristics were similar to the rest of AHOD. Overall incidence was 12.5 per 100 person-years. Chlamydial infections increased from 3.4 per 100 person-years (95% confidence interval (CI): 1.9–5.7) in 2005 to 6.7 per 100 person-years (95% CI: 4.5–9.5) in 2011, peaking in 2010 (8.1 per 100 person-years 95% CI: 5.6–11.2). Cases were distributed among rectal (61.9%), urethral (34%) and pharyngeal (6.3%) sites. Gonococcal infections increased, peaking in 2010 (4.7 per 100 person-years 95% CI: 5.6–11.2 Ptrend = 0.0099), distributed among rectal (63.9%), urethral (27.9%) and pharyngeal (14.8%) sites. Syphilis showed several peaks, the largest in 2008 (5.3 per 100 person-years 95% CI: 3.3–8.0) the overall trend was not significant (P = 0.113). Genital warts declined from 7.5 per 100 person-years (95% CI: 4.8–11.3) in 2005 to 2.4 per 100 person-years (95% CI: 1.1–4.5) in 2011 (Ptrend = 0.0016). Conclusions: For chlamydial and gonococcal infections, incidence was higher than previous Australian estimates among HIV-infected men who have sex with men, increasing during 2005–2011. Rectal infections outnumbered infections at other sites. Syphilis incidence remained high but did not increase that of genital warts was lower and decreased.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Public Library of Science (PLoS)
Date: 02-06-2011
Publisher: Wiley
Date: 06-09-2016
DOI: 10.1111/HIV.12312
Publisher: Springer Science and Business Media LLC
Date: 11-11-2020
DOI: 10.1186/S12879-020-05563-W
Abstract: Bacterial vaginosis (BV) is estimated to affect 1 in 3 women globally and is associated with obstetric and gynaecological sequelae. Current recommended therapies have good short-term efficacy but 1 in 2 women experience BV recurrence within 6 months of treatment. Evidence of male carriage of BV-organisms suggests that male partners may be reinfecting women with BV-associated bacteria (henceforth referred to as BV-organisms) and impacting on the efficacy of treatment approaches solely directed to women. This trial aims to determine the effect of concurrent male partner treatment for preventing BV recurrence compared to current standard of care. StepUp is an open-label, multicentre, parallel group randomised controlled trial for women diagnosed with BV and their male partner. Women with clinical-BV defined using current gold standard diagnosis methods (≥3 Amsel criteria and Nugent score (NS) = 4–10) and with a regular male partner will be assessed for eligibility, and couples will then be consented. All women will be prescribed oral metronidazole 400 mg twice daily (BID) for 7 days, or if contraindicated, a 7-day regimen of topical vaginal 2% clindamycin. Couples will be randomised 1:1 to either current standard of care (female treatment only), or female treatment and concurrent male partner treatment (7 days of combined antibiotics - oral metronidazole tablets 400 mg BID and 2% clindamycin cream applied topically to the glans penis and upper shaft [under the foreskin if uncircumcised] BID). Couples will be followed for up to 12 weeks to assess BV status in women, and assess the adherence, tolerability and acceptability of male partner treatment. The primary outcome is BV recurrence defined as ≥3 Amsel criteria and NS = 4–10 within 12 weeks of enrolment. The estimated s le size is 342 couples, to detect a 40% reduction in BV recurrence rates from 40% in the control group to 24% in the intervention group within 12 weeks. Current treatments directed solely to women result in unacceptably high rates of BV recurrence. If proven to be effective the findings from this trial will directly inform the development of new treatment strategies to impact on BV recurrence. The trial was prospectively registered on 12 February 2019 on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000196145, Universal Trial Number: U1111–1228-0106, www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376883& isReview=true ).
Publisher: Oxford University Press (OUP)
Date: 19-01-2022
DOI: 10.1093/OFID/OFAC029
Abstract: Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. Of 29 340 in iduals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36–51). Overall, 13 950 (48%) in iduals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2 IQR, 3.9–7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU 95% confidence interval [CI], 6.3–7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi’s sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89–1.49], & –12 months 0.97 [95% CI, 0.71–1.32], & –24 months 0.84 [95% CI, 0.64–1.11], & –36 months 1.10 [95% CI, 0.82–1.47], & months 0.90 [95% CI, 0.65–1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P & .0001). Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2006
DOI: 10.1097/01.QAI.0000219779.50668.E6
Abstract: Structured treatment interruptions (STIs) have been postulated to improve virologic control in primary HIV infection (PHI) by stimulating HIV-specific T-lymphocyte immunity. The addition of hydroxyurea (HU) may reduce viral production from activated CD4 cells. Patients with PHI received a standardized antiretroviral (ARV) regimen consisting of indinavir 800 mg twice daily (BID), ritonavir 100 mg BID, didanosine 400 mg (QD), and either stavudine 40 mg BID or lamivudine 150 mg BID, for up to 12 months and were randomized to HU 500 mg BID or not. If viral suppression (<50 copies/mL) was achieved, up to 3 STIs were undertaken. Two ARV cycles were allowed after each interruption if virologic rebound to more than 5000 RNA copies/mL occurred. Treatment success was defined as maintaining viral loads below 5000 copies/mL for 6 months after ARV interruption. Sixty-eight male homosexual patients were randomized: 35 to ARV + HU and 33 to ARV-alone. Median baseline HIV RNA was 5.73 log10 copies/mL, and median CD4 T-lymphocyte count was 517 cells/microL. Treatment success was not significantly different between those receiving and not receiving HU, with 9 (26%) and 9 (27%), respectively, maintaining viral load at less than 5000 copies/mL in each group (P = 0.88). Virologic control was achieved by 11 (19%) of 59 after 1 STI, 1 (2%) of 41 after 2 STIs, and 6 (17%) of 36 after the third STI. Serious adverse events were recorded for 9 (26%) of 35 of patients using HU and 3 (9%) of 33 in the ARV-only group (P = 0.28). CD4 cell increases were significantly blunted for the HU group compared to the ARV-alone group after the initial treatment phase (+101 cells vs. +196 cells, respectively, P = 0.006). Hydroxyurea was not found to be beneficial when used in association with STIs in patients during PHI.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Mary Ann Liebert Inc
Date: 06-2009
Abstract: It is not fully elucidated whether patients who receive antiretroviral therapy (ART) can maintain continued CD4 count increases. Previous studies suggested a plateau 2-4 years after treatment initiation. We aimed to characterize the evolution of CD4 counts in HIV-infected in iduals receiving long-term suppressive ART, by performing a retrospective study of patients who maintained viral suppression (HIV RNA or =5 years. We used linear regression models to determine for each in idual whether the CD4 count continued to increase or plateau. Furthermore, we estimated whether the slope of the CD4 count for each in idual became zero, which we defined as the CD4 set-point. We assessed factors associated with continued CD4 count rise, reaching a CD4 set-point and time to the CD4 set-point. Fifty-nine patients were included. The median baseline CD4 count was 238 (IQR, 120-360) cells/microl and the median duration on ART was 7.6 (IQR, 5.9-9.3) years. On ART, CD4 count continued to increase in 37 subjects (63%). Significant predictors of continued CD4 count increase included a lower baseline log10 HIV RNA (OR, 0.35 95% CI, 0.14-0.89 p=0.026) and a shorter duration on ART (OR, 0.65 95% CI, 0.47-0.91 p=0.021). Twenty-four (41%) subjects reached a set-point after a median 4.3 (IQR 1.8-6.4) years on ART. A lower baseline CD4 percentage was associated with both a longer time to reach the CD4 set-point and a lower CD4 count at the CD4 set-point. These findings suggest that CD4 count may continue to increase in some patients after several years of ART. Our results point to an advantage to commencing ART at higher CD4+ T cell strata. These data should be considered when estimating the optimal time to initiate ART.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-05-2013
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/SH10008
Abstract: Background Patients who have become triple class experienced (TCE) are at a high risk of exhausting available treatment options. This study aims to investigate factors associated with becoming TCE and to explore the effect of becoming TCE on survival. We also project the prevalence of TCE in Australia to 2012. Methods: Patients were defined as TCE when they stopped a combination antiretroviral treatment (cART) that introduced the third of the three major antiretroviral classes. Cox proportional hazards models were used to investigate factors associated with TCE and the effect of TCE on survival. To project TCE prevalence, we used predicted rates of TCE by fitting a Poisson regression model, together with the estimated number of patients who started cART in each year in Australia, assuming a mortality rate of 1.5 per 100 person-years. Results: Of the 1498 eligible patients, 526 became TCE. Independent predictors of a higher risk of TCE included current CD4 counts below 200 cells μL–1 and earlier calendar periods. No significant difference in survival was observed between those who were TCE and those who were not yet TCE. An increasing number of patients are using cART in Australia and if current trends continue, the number of patients who are TCE is estimated to increase from 2800 in 2003 to 5000 in 2012. Conclusion: Our results suggest that the prevalence of TCE in Australia is estimated to plateau after 2003. However, as an increasing number of patients are becoming TCE, it is necessary to develop new drugs that come from new classes or do not have overlapping resistance.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-08-2012
Publisher: Wiley
Date: 16-03-2023
DOI: 10.1111/HIV.13483
Abstract: Multimorbidity is common among people living with HIV (PLWH), with numerous cross‐sectional studies demonstrating associations with older age and past immunosuppression. Little is known about the progression of multimorbidity, particularly in the setting of long‐term access to antiretrovirals. This study aims to determine factors predictive of change in multimorbidity in PLWH. People living with HIV who attended a regional HIV service were recruited to a consented observational cohort between September 2016 and March 2020. Demographic data, laboratory results and a Cumulative Illness Rating Scale (CIRS) were collected at enrolment and first clinical review of every subsequent year. Change in CIRS score was calculated from enrolment to February 2021. Associations with change were determined through univariate and multivariate linear regression. Of 253 people, median age was 58.9 [interquartile range (IQR): 51.9–64.4] years, 91.3% were male, and HIV was diagnosed a median of 22.16 years (IQR: 12.1–30.9) beforehand. Length of time in the study was a median of 134 weeks (IQR: 89.0–179.0), in which a mean CIRS score change of 1.21 (SD 2.60) was observed. Being older ( p 0.001) and having a higher body mass index ( p = 0.008) and diabetes ( p = 0.014) were associated with an increased likelihood of worsening multimorbidity. PLWH with a higher level of multimorbidity at baseline were less likely to worsen over time ( p 0.001). As diabetes and weight predict worsening multimorbidity, routine diabetes screening, body mass index measurement, and multimorbidity status awareness are recommended.
Publisher: Elsevier BV
Date: 2018
DOI: 10.2139/SSRN.3269607
Publisher: Informa UK Limited
Date: 15-04-2022
Publisher: Wiley
Date: 29-07-2018
DOI: 10.1111/NEP.13100
Publisher: Wiley
Date: 19-02-2009
DOI: 10.1111/J.1468-1293.2008.00667.X
Abstract: Poly-l-lactic acid (PLA) injections modestly increase objectively assessed facial thickness but not facial soft tissue volume (FSTV) over 24 weeks. The durability of this response has not been well defined objectively. HIV-infected lipoatrophic adults were randomized to four open-label PLA treatments administered every 2 weeks from week 0 (immediate group, n=50) or from week 24 (deferred group, n=50). Endpoints included FSTV assessed by computed tomography, facial lipoatrophy severity, quality of life (QoL) and safety. Analyses were by intention to treat. Between weeks 24 and 48, soft tissue thickness increased modestly in injection planes, at the maxillary [mean 0.9 mm 95% confidence interval (CI) 0.3-1.5 mm P=0.007] and base of nasal septum levels (mean 0.4 mm 95% CI 0.1-0.8 P=0.021), but not in untreated areas (P=0.79 and P=0.24). PLA durability assessed at week 48 in immediate group participants showed a mean change in FSTV of 14 cm(3) (95% CI-1 to 29 cm(3) P=0.060) and increased tissue depth at the maxillary (P<0.0001), base of nasal septum (P<0.0001) and mandibular (P=0.0035) levels. At week 48, clinicians and patients subjectively assessed facial lipoatrophy severity as reduced in immediate participants (83 and 91%, respectively), and the Mental Health scale score of the Short Form-36 Health Survey improved significantly in immediate participants relative to deferred participants (P=0.027). Subcutaneous injection-site nodule incidence at 48 weeks was 10%. PLA treatment benefits were durable, with objectively assessed modest increases in facial volume and tissue thickness sustained over 48 weeks in injection planes but not in other facial areas. Improvements in some QoL domains were maintained.
Publisher: SAGE Publications
Date: 19-02-2013
Abstract: The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm 3 in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-02-2012
DOI: 10.1002/HEP.24754
Publisher: Oxford University Press (OUP)
Date: 04-10-2020
DOI: 10.1093/CID/CIZ985
Abstract: Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94). High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. NCT02102451.
Publisher: Elsevier BV
Date: 03-2010
Publisher: Oxford University Press (OUP)
Date: 18-04-2016
DOI: 10.1093/CID/CIW236
Publisher: Wiley
Date: 19-02-2009
DOI: 10.1111/J.1468-1293.2008.00663.X
Abstract: The aim of the study was to determine the effect of nucleoside reverse transcriptase inhibitors (NRTIs) on CD4 recovery in HIV-1-infected in iduals receiving long-term suppressive combination antiretroviral therapy (cART). A retrospective cohort study was carried out. The mean time-weighted CD4 change from baseline was determined at weeks 48, 96 and 144: its associations with exposure to NRTIs were assessed using linear regression. One hundred and five patients were included. Their median baseline CD4 count was 225 (interquartile range 91-362) cells/microL. A trend of greater CD4 change from baseline was observed for in iduals who at baseline had CD4 counts >200 cells/microL (138 vs. 113, 176 vs. 134 and 204 vs. 173 cells/microL), or were 0.05. Lower CD4 increases were observed in patients exposed to didanosine (ddI) or a combination of ddI and stavudine, although the difference was not statistically significant. For patients that commenced cART with CD4 count </=200 cells/microL, a trend towards a CD4 count response <250 cells/microL at weeks 48, 96 and 144 was observed in patients receiving zidovudine. Exposure to different NRTIs in initial cART was not significantly associated with variable rises in CD4 cell count. However, these findings need to be confirmed in larger studies.
Publisher: Wiley
Date: 2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2002
DOI: 10.1097/00007435-200211000-00006
Abstract: Self-collected s les have been shown to be an acceptable and sensitive method for the detection by polymerase chain reaction (PCR) of sexually transmitted infections (STIs) among women. GOAL The goal of the study was to compare self-collected s ling methods to conventional practitioner endocervical s ling for the PCR detection of Chlamydia trachomatis and Neisseria gonorrhoeae to compare two self-collected s ling methods for the detection of T vaginalis by PCR. Women (n = 318) from urban and remote areas of central Australia participated in the study when attending their health clinic for a check-up. They each provided a FVU s le, self-collected vaginal swab specimen, and t on specimen. This was followed by a clinical examination by a practitioner, with collection of endocervical and high vaginal swabs for testing by conventional microscopy and culture for N gonorrhoeae and T vaginalis, respectively. The FVU, self-collected vaginal swab, t on, and endocervical swab specimens were tested by Roche Cobas Amplicor for C trachomatis and N gonorrhoeae. The self-collected vaginal swab and t on specimens were also tested by an in-house PCR method for the detection of T vaginalis. In toto, C trachomatis was detected by PCR in 11.5%, N gonorrhoeae in 11.8%, and T vaginalis in 24.6%. Molecular diagnostics for N gonorrhoeae and T vaginalis were significantly more sensitive than traditional assays with microscopy and culture. For the detection of C trachomatis by PCR, t ons were the most sensitive (100.0%) and urine the least sensitive (72.7%) specimens ( = 0.01). For the detection of by PCR, the self-collected t on was the most sensitive specimen, followed by the endocervical swab, self-collected swab, and urine specimen, with sensitivities of 97.2%, 92.6%, 71.9%, and 31.2%, respectively. For detection of N gonorrhoeae, statistically significant differences were detected for urine versus t on ( < 0.0001), endocervical swab ( < 0.001), and self-collected swab ( = 0.01) and for self-collected swab versus t on ( = 0.01). Subsequent data collection showed that sensitivity of urine PCR for detection of N gonorrhoeae improved with freezing of urine specimens and shorter transport time. T ons were also more sensitive than self-collected swabs for detection of T vaginalis (sensitivity of 100% versus 87.7%). Self-collected specimens offer women in remote communities an acceptable and sensitive alternative method of testing for STIs. The low sensitivity of N gonorrhoeae PCR of urine specimens may reflect poor transport and storage conditions, which we have shown can be improved by freezing urine specimens and reducing transport delays.
Publisher: Wiley
Date: 07-2003
DOI: 10.1046/J.1468-1293.2003.00152.X
Abstract: To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART). Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti-HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan-Meier survival curves and Cox proportional hazard model of time to AIDS events and death. Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV-only patients in terms of AIDS-free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/microL (95% CI 1-67) less than HIV-only patients. Coinfection with HBV or HCV is relatively common among HIV-infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-02-2018
Publisher: Public Library of Science (PLoS)
Date: 17-02-2023
DOI: 10.1371/JOURNAL.PONE.0282001
Abstract: The effect of long-term exposure to antiretroviral therapy (ART) on hypertension in sub-Saharan Africa remains unclear. We aimed to determine the prevalence and incidence of hypertension in people living with HIV (PLWH) with more than 10 years of ART in Uganda. The analysis was performed within a cohort of adult PLWH with more than 10 years of ART at an HIV clinic in K ala, Uganda. Participants were eligible for this analysis if they had ≥2 follow-up visits. Hypertension was defined as two consecutive systolic blood pressure (SBP) measures greater than 140 mmHg and/or diastolic blood pressure (DBP) greater than 90 mmHg, and/or documented diagnosis and/or the initiation of antihypertensives. We determined the proportion of PLWH with hypertension at baseline and used multivariable logistic regression to determine the factors associated with prevalent hypertension. To determine the incidence of hypertension, follow-up began from the cohort baseline date and was censored at the last clinic visit or date of the event, whichever occurred earlier. Multivariable Poisson regression was used to determine the adjusted incidence rate ratios (aIRR) of hypertension according to demographic, ART, and clinical characteristics. Of the 1000 ALT participants, 970 (97%) had ≥2 follow-up visits, and 237 (24.4%) had hypertension at baseline. The odds of prevalent hypertension were 1.18 for every 5-year increase in age (adjusted odds ratio (aOR) 1.18, 95% CI 1.10–1.34) and were higher among males (aOR 1.70, 95% CI 1.20–2.34), participants with diabetes mellitus (aOR 2.37, 95% CI 1.10–4.01), obesity (aOR 1.99, 95% CI 1.08–3.60), high cholesterol (aOR 1.47, 95% CI 1.16–2.01), and those with prior exposure to stavudine (aOR 2.10, 95% CI 1.35–3.52), or nevirapine (aOR 1.90, 95% CI 1.25–3.01). Of the 733 participants without hypertension at baseline, 116 (15.83%) developed hypertension during 4671.3 person-years of follow-up (incidence rate 24.8 per 1000 person-years 95% CI 20.7–29.8). The factors associated with incident hypertension were obesity (adjusted incidence rate ratio (aIRR) 1.80, 95% CI 1.40–2.81), older age (aIRR 1.12 per 5-year increase in age, 95% CI 1.10,1.25), and renal insufficiency (aIRR1.80, 95% CI 1.40–2.81). The prevalence and incidence of hypertension were high in this heavily treated PLWH cohort. Therefore, with increasing ART coverage, HIV programs in SSA should strengthen the screening for hypertension in heavily treated PLWH.
Publisher: Oxford University Press (OUP)
Date: 21-10-2019
DOI: 10.1093/JAMIA/OCZ183
Abstract: To investigate the relationship between emotion sharing and technically troubled dialysis (TTD) in a remote patient monitoring (RPM) setting. A custom software system was developed for home hemodialysis patients to use in an RPM setting, with focus on emoticon sharing and sentiment analysis of patients’ text data. We analyzed the outcome of emoticon and sentiment against TTD. Logistic regression was used to assess the relationship between patients’ emotions (emoticon and sentiment) and TTD. Usage data were collected from January 1, 2015 to June 1, 2018 from 156 patients that actively used the app system, with a total of 31 159 dialysis sessions recorded. Overall, 122 patients (78%) made use of the emoticon feature while 146 patients (94%) wrote at least 1 or more session notes for sentiment analysis. In total, 4087 (13%) sessions were classified as TTD. In the multivariate model, when compared to sessions with self-reported very happy emoticons, those with sad emoticons showed significantly higher associations to TTD (aOR 4.97 95% CI 4.13–5.99 P = & .001). Similarly, negative sentiments also revealed significant associations to TTD (aOR 1.56 95% CI 1.22–2 P = .003) when compared to positive sentiments. The distribution of emoticons varied greatly when compared to sentiment analysis outcomes due to the differences in the design features. The emoticon feature was generally easier to understand and quicker to input while the sentiment analysis required patients to manually input their personal thoughts. Patients on home hemodialysis actively expressed their emotions during RPM. Negative emotions were found to have significant associations with TTD. The use of emoticons and sentimental analysis may be used as a predictive indicator for prolonged TTD.
Publisher: Mary Ann Liebert Inc
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 03-01-2019
Publisher: CSIRO Publishing
Date: 2018
DOI: 10.1071/SH16237
Abstract: Background The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia’s ‘universal access’ health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme. Methods: A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed. Input data came from a cohort of 180 HIV-positive temporary residents living in Australia who are receiving free ART donated by pharmaceutical companies for up to 4 years. Results: Expanding ART access to an estimated total 450 HIV+ temporary residents in Australia for 5 years could avert 80 new infections. The model estimated the total median discounted (5%) cost for ART and associated care to be A$36 million, while the total savings in lifetime-discounted costs for the new infections averted was A$22 million. Conclusions: It is estimated that expanded access to ART for all HIV-positive temporary residents in Australia will substantially reduce HIV transmission to their sexual partners at little additional cost. In the context of Australia’s National HIV strategy and Australia’s endorsement of global goals to provide universal access to ART for all people with HIV, this is an important measure to remove inequities in the provision of HIV-related treatment and care.
Publisher: Massachusetts Medical Society
Date: 20-11-2003
DOI: 10.1056/NEJMOA030218
Publisher: Elsevier BV
Date: 10-2015
Publisher: SAGE Publications
Date: 10-2015
DOI: 10.3851/IMP2916
Abstract: Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care, which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high-resource setting. Rates of LTFU were measured in the Australian HIV Observational Database for a range of patient characteristics. Multivariate repeated measures regression methods were used to identify determinants of LTFU. Mortality by LTFU status was ascertained using linkage to the National Death Index. Survival following combination antiretroviral therapy initiation was investigated using the Kaplan–Meier (KM) method and Cox proportional hazards models. Of 3,413 patients included in this analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment. Multivariate predictors of LTFU included viral load (VL) ,000 copies/ml (rate ratio [RR] 1.63 95% CI 1.45, 1.84 ref ≤400), time under follow-up (per year RR 1.03 95% CI 1.02, 1.04) and prior LTFU (per episode RR 1.15 95% CI 1.06, 1.24). KM curves for survival were similar by LTFU status ( P=0.484). LTFU was not associated with mortality in Cox proportional hazards models (univariate hazard ratio [HR] 0.93 95% CI 0.69, 1.26) and multivariate HR 1.04 (95% CI 0.77, 1.43). Increased risk of LTFU was identified amongst patients with potentially higher infectiousness. We did not find significant mortality risk associated with LTFU. This is consistent with timely re-engagement with treatment, possibly via high levels of unreported linkage to other health-care providers.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 07-2010
Publisher: CSIRO Publishing
Date: 12-09-2022
DOI: 10.1071/SH22085
Abstract: Background As people living with HIV now have a life expectancy approaching that of the general population, clinical care focuses increasingly on the management and prevention of comorbidities and conditions associated with aging. We aimed to assess the prevalence of physical function (PF) limitation among gay and bisexual men (GBM) and determine whether HIV is associated with severe PF limitation in this population. Methods We analysed cross-sectional data from GBM aged ≥55 years in the Australian Positive and Peers Longevity Evaluation Study who completed a self-administered survey on health and lifestyle factors. PF was measured using the Medical Outcomes Study–Physical Functioning scale. Factors associated with severe PF limitation were assessed using logistic regression. Results The survey was completed by 381 men: 186 without HIV and 195 with HIV. Median age was 64.3 years for GBM without HIV and 62.1 years for GBM with HIV. Compared with men without HIV, those with HIV had higher proportions of severe (13.3% vs 8.1%) and moderate-to-severe (26.7% vs 24.2%) PF limitation. Severe PF limitation commonly involved difficulty with vigorous activity (95% with severe PF limitation described being limited a lot), climbing several flights of stairs (68.4% limited a lot), bending, kneeling or stooping (60.5% limited a lot), and walking 1 km (55.0% limited a lot). In a model adjusted for age, body mass index, typical duration of physical activity, psychological distress, and number of comorbidities, we found a significant association between HIV and severe PF limitation (adjusted odds ratio 3.3 vs not having HIV, 95% confidence interval 1.3–8.7). Conclusions The biological mechanisms underlying this association require further investigation, particularly given the growing age of the HIV population and inevitable increase in the burden of PF limitation.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2015
Publisher: Wiley
Date: 2015
Publisher: Public Library of Science (PLoS)
Date: 28-06-2013
Publisher: Mary Ann Liebert Inc
Date: 11-2018
Publisher: Public Library of Science (PLoS)
Date: 31-12-2020
DOI: 10.1371/JOURNAL.PONE.0243625
Abstract: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only in iduals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL. Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) in iduals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p .001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p .001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04). In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2011
Publisher: Elsevier BV
Date: 07-2011
Publisher: Mary Ann Liebert Inc
Date: 10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2017
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/SH15037
Abstract: Gay and other men who have sex with men (GMSM) are disproportionally affected by the HIV epidemic in Australia. The study objective is to combine a clinical-based cohort with a community-based surveillance system to present a broader representation of the GMSM community to determine estimates of proportions receiving antiretroviral therapy (ART) and/or with an undetectable viral load. Between 2010 and 2012, small increases were shown in ART uptake (to 70.2%) and proportions with undetectable viral load (to 62.4%). The study findings highlight the potential for significantly increasing ART uptake among HIV-positive GMSM to reduce the HIV epidemic in Australia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-04-2020
DOI: 10.1002/HEP.31003
Abstract: Among treatment‐naive in iduals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir ibrentasvir for 8 weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir ibrentasvir for 6 weeks in people with acute and recent HCV infection. In this open‐label, single‐arm, multicenter, international pilot study, adults with recent HCV (duration of infection 12 months) received glecaprevir ibrentasvir 300/120 mg daily for 6 weeks. Primary infection was defined by first positive anti‐HCV antibody and/or HCV RNA within 6 months of enrollment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or alanine aminotransferase 10 × upper limit of normal) or anti‐HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months of enrollment and evidence of prior spontaneous or treatment‐induced clearance. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Thirty men (median age 43 years, 90% men who have sex with men) received treatment, of whom 77% (n = 23) were human immunodeficiency virus–positive, 47% (n = 14) had ever injected drugs, and 13% (n = 4) had HCV reinfection. The majority had HCV genotype 1 (83%, n = 25), followed by genotype 4 (10%, n = 3) and genotype 3 (7%, n = 2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log 10 IU/mL (range 0.9, 7.7). SVR12 in the intention‐to‐treat and per‐protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse, and there were two cases of nonvirological failure (death, n = 1 loss to follow‐up, n = 1). No treatment‐related serious adverse events were seen. Glecaprevir ibrentasvir for 6 weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened‐duration pan‐genotypic therapy in this setting.
Publisher: Oxford University Press (OUP)
Date: 26-03-2013
DOI: 10.1093/CID/CIT196
Publisher: Public Library of Science (PLoS)
Date: 20-11-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Wiley
Date: 06-2018
DOI: 10.1111/IMJ.13733
Abstract: Multimorbidity and unplanned admissions are common among people with human immunodeficiency virus (PWH). To determine factors predictive of unplanned admission among PWH in regional New South Wales and compare care coordination between people with and without unplanned admissions. A prospective cohort study of PWH attending a regional human immunodeficiency virus (HIV) service was conducted. Baseline HIV-specific results and multimorbidity markers including Cumulative Illness Rating Scale (CIRS) were assessed as predictors of time to first unplanned admission using Cox regression analysis. Care coordination markers were compared between people with and without unplanned admission, using χ A cohort of 181 PWH was followed for a maximum of 5 years. During a total of 739 person-years of follow up, 39 (20.6%) patients reached the endpoint of unplanned admission. In multivariate analysis, the baseline CIRS score was predictive of unplanned admission (P < 0.001). Age, HIV-specific markers and missed visits were not predictive of unplanned admission. For patients with an unplanned admission, discharge summaries were documented for 22/39 (56.4%). Of 180 PWH with a visit after baseline, 131 (72.8%) had a letter to a general practitioner and 79 (43.7%) had two or more prescribers. Having two or more prescribers was more common in people with an unplanned admission than in those without (64.1% vs 38.0%, P = 0.004). Unplanned admission among PWH is predicted by multimorbidity. Care for PWH should include coordinated management of other health conditions in order to reduce their severity and prevent unplanned admissions.
Publisher: Wiley
Date: 08-07-2014
DOI: 10.1002/JMV.24010
Publisher: BMJ
Date: 02-2022
DOI: 10.1136/BMJOPEN-2021-059968
Abstract: Vaccines against human papillomavirus (HPV) are the key to controlling cervical cancer in low/middle-income countries (LMICs) where incidence is highest, but there have been limited data from these settings on programme impact on HPV prevalence, and none in a population with endemic HIV infection. Furthermore, for many LMICs, the currently recommended two-dose schedule is difficult to deliver at scale, so there is mounting interest in a single-dose schedule. The H uman Papillomavirus O ne and Two-Dose P opulation E ffectiveness Study is a hybrid impact evaluation of the national South African HPV vaccination programme, which has targeted grade 4 girls aged at least 9 years in public schools with two doses of vaccine since 2014, and a single-dose vaccine ‘catch-up’ programme delivered in one district in 2019. Impacts of both schedules on the prevalence of type-specific HPV infection will be measured using repeat cross-sectional surveys in adolescent girls and young women aged 17–18 years recruited at primary healthcare clinics in the four provinces. A baseline survey in 2019 measured HPV prevalence in the cohort who were ineligible for vaccination because they were already above the target age or grade under either the national programme or the single-dose programme in the selected district. HPV prevalence surveys are repeated in 2021 in the selected district, and in 2023 in all four provinces. We will calculate prevalence ratios to compare the prevalence of HPV types 16 and 18 in the single-dose (2021) and two-dose (2023) cohorts, with the vaccine-ineligible (2019) cohort. The project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC #181005), and the University of New South Wales HREC (#181-005). Findings will be disseminated through peer-reviewed journals, scientific meetings, reports and community forums.
Publisher: Public Library of Science (PLoS)
Date: 29-08-2018
Publisher: Public Library of Science (PLoS)
Date: 11-04-2014
Publisher: Wiley
Date: 23-01-2017
DOI: 10.1111/JVH.12666
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/SH14070
Abstract: Background Multimorbidity is the co-occurrence of more than one chronic health condition in addition to HIV. Higher multimorbidity increases mortality, complexity of care and healthcare costs while decreasing quality of life. The prevalence of and factors associated with multimorbidity among HIV positive patients attending a regional sexual health service are described. Methods: A record review of all HIV positive patients attending the service between 1 July 2011 and 30 June 2012 was conducted. Two medical officers reviewed records for chronic health conditions and to rate multimorbidity using the Cumulative Illness Rating Scale (CIRS). Univariate and multivariate linear regression analyses were used to determine factors associated with a higher CIRS score. Results: One hundred and eighty-nine in iduals were included in the study the mean age was 51.8 years and 92.6% were men. One-quarter (25.4%) had ever been diagnosed with AIDS. Multimorbidity was extremely common, with 54.5% of in iduals having two or more chronic health conditions in addition to HIV the most common being a mental health diagnosis, followed by vascular disease. In multivariate analysis, older age, having ever been diagnosed with AIDS and being on an antiretroviral regimen other than two nucleosides and a non-nucleoside reverse transcriptase inhibitor or protease inhibitor were associated with a higher CIRS score. Conclusion: To the best of our knowledge, this is the first study looking at associations with multimorbidity in the Australian setting. Care models for HIV positive patients should include assessing and managing multimorbidity, particularly in older people and those that have ever been diagnosed with AIDS.
Publisher: Public Library of Science (PLoS)
Date: 07-11-2012
Publisher: SAGE Publications
Date: 11-2017
DOI: 10.3851/IMP3155
Abstract: In the era of effective antiretroviral treatment (ART) CD4:CD8 ratio is proposed as a potential marker for HIV-positive (HIV+) patients at increased risk for non-AIDS comorbidities. The current study aims to compare CD4:CD8 ratio between Asian and Caucasian HIV+ patients. HIV+ patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) meeting specific criteria were included. In these analyses Asian and Caucasian status were defined by cohort. Factors associated with a low CD4:CD8 ratio (cutoff .2) prior to ART commencement, and with achieving a normal CD4:CD8 ratio ( ) at 12 and 24 months post ART commencement were assessed using logistic regression. There were 591 patients from AHOD and 2,620 patients from TAHOD who met the inclusion criteria. TAHOD patients had a significantly ( P .001) lower odds of having a baseline (prior to ART initiation) CD4:CD8 ratio greater than 0.2. After 12 months of ART, AHOD patients were more than twice as likely to achieve a normal CD4:CD8 ratio compared to TAHOD patients (15% versus 6%). However, after adjustment for confounding factors there was no significant difference between cohorts in the odds of achieving a CD4:CD8 ratio ( P=0.475). We found a significantly lower CD4:CD8 ratio prior to commencing ART in TAHOD compared to AHOD even after adjusting for confounders. However, after adjustment, there was no significant difference between the cohorts in odds of achieving normal ratio. Baseline CD4 + and CD8 + counts seem to be the main driver for this difference between these two populations.
Publisher: Wiley
Date: 23-03-2007
DOI: 10.1111/J.1468-1331.2007.01686.X
Abstract: We performed a retrospective review of cases of human immunodeficiency virus-associated progressive multifocal leucoencephalopathy in four hospitals (three in Australia and one in Hong Kong) between 1987 and 2003 in order to describe the local experience with this disease and to evaluate parameters impacting upon survival. Eighty-seven cases were identified and demographic details, baseline parameters and treatment methods and response were described. Survival was substantially increased in the post-highly active antiretroviral therapy (HAART) era with a median survival increase from 14 to 64 weeks. On multivariate analysis, variables associated with prolonged survival included a CD4 count of >100 cells/mul at diagnosis and the use of HAART post-diagnosis, with no significant additional advantage from the use of neuroactive antiretrovirals.
Publisher: Oxford University Press (OUP)
Date: 14-06-2018
DOI: 10.1093/CID/CIY508
Abstract: Cancers are a major source of morbidity and mortality for human immunodeficiency virus (HIV)-infected persons, but the clinical benefits of smoking cessation are unknown. Participants were followed from 1 January 2004 until first cancer diagnosis, death, or 1 February 2016. Smoking status was defined as ex-smoker, current smoker, and never smoker. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression, adjusting for demographic and clinical factors. In total 35442 persons from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study contributed 309803 person-years of follow-up. At baseline, 49% were current smokers, 21% were ex-smokers, and 30% had never smoked. Incidence of all cancers combined (n = 2183) was highest <1 year after smoking cessation compared to never smokers (aIRR, 1.66 [95% confidence interval {CI}, 1.37-2.02]) and not significantly different from never smokers 1-1.9 years after cessation. Lung cancer incidence (n = 271) was elevated 5 years after smoking cessation. Deterring uptake of smoking and smoking cessation efforts should be prioritised to reduce future cancer risk.
Publisher: Wiley
Date: 13-05-2016
DOI: 10.1002/CNCY.21730
Abstract: In a cytology-based screening program intended to prevent anal cancer, the anal transformation zone (TZ) should be adequately s led because it is the site most susceptible to the development of the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). An adequate TZ component is defined as comprising at least 10 rectal columnar or squamous metaplastic cells. In the current study, the authors examined whether the presence of a TZ component in anal cytology correlated with the detection of histological HSIL. In a natural history study of anal human papillomavirus infection in homosexual men, all participants underwent liquid-based cytology and high-resolution anoscopy (HRA) with or without biopsy at each visit. True-negative cytology (negative cytology with non-HSIL biopsy or negative HRA), false-negative cytology (negative cytology with HSIL biopsy), and true-positive cytology (abnormal cytology with HSIL biopsy) were compared with regard to the presence or absence of a TZ component. Of 617 participants, baseline results included 155 true-positive results, 191 true-negative results, and 31 false-negative results. The absence of an adequate TZ component was found to be significantly higher for false-negative (32.3%) than for either true-positive (11.0% P = .0034) or true-negative (13.1% P = .0089) results. Significantly more false-negative cases lacked a TZ component compared with either true-positive or true-negative cases. TZ cells may be an important indicator of s le quality for anal cytology because, unlike cervical s ling, the anal canal is not visualized during cytology s ling. Cancer Cytopathol 2016 :596-601. © 2016 American Cancer Society.
Publisher: Oxford University Press (OUP)
Date: 15-03-2010
DOI: 10.1086/650743
Abstract: Neurocognitive impairment remains prevalent, despite combination antiretroviral therapy (cART). Differences between changes in cerebral function and alternative cARTs have not been prospectively assessed. Treatment-naive, HIV-1-infected in iduals randomly allocated to commence cART (tenofovir-emtricitabine plus either efavirenz [arm 1], atazanavir-ritonavir [arm 2], or zidovudine-abacavir [arm 3]) were eligible. Cerebral function tests included neurocognitive testing and assessment of cerebral metabolites using proton magnetic resonance spectroscopy in several anatomical voxels, including right frontal white matter and right basal ganglia, at baseline and after 48 weeks. N-acetylaspartate-to-creatine (NAA/Cr) ratios were calculated. Both the differences between changes in neurocognitive function and NAA/Cr ratios over 48 weeks and the study arms (arm 1 vs arm 2 arm 1 vs arm 3) were assessed. Thirty subjects completed study procedures (9, 9, and 12 subjects in arms 1, 2, and 3, respectively). Mean CD4+ cell counts (+/- standard deviation) were 218 +/- 87 cells/microL at baseline and 342 +/- 145 cells/microL at week 48. The mean plasma HIV-1 RNA level was <50 copies/mL for 28 of the 30 subjects at week 48. Over 48 weeks, greater improvements in identification reaction time (P = .04) and executive function (P = .02) were observed in arm 3, compared with arm 1 (0.03, -0.30, -0.50 log10 ms change in identification reaction time, in arms 1, 2, and 3, respectively). Increases in the NAA/Cr ratio were observed in all voxels (maximum 38% in right basal ganglia), with greater increases observed in arm 1 than in arm 2 (P = .03) in frontal white matter (30%, -7%, and 0% change in the NAA/Cr ratio, in arms 1, 2, and 3, respectively). To our knowledge, this is the first study to prospectively describe different changes in cerebral function testing parameters between different cARTs. Greater improvements in neuronal recovery (NAA/Cr ratio) were observed for recipients of tenofovir-emtricitabine plus efavirenz (arm 1), and greater improvements in neurocognitive function testing were observed for recipients of tenofovir-emtricitabine plus zidovudine-abacavir (arm 3).
Publisher: SAGE Publications
Date: 07-2015
DOI: 10.3851/IMP3035
Abstract: In iduals with recent HCV infection may benefit from shortened duration therapy. These studies evaluated the efficacy and safety of response-guided regimens with pegylated interferon-α2a and ribavirin for people with recent HCV infection. Participants with recent hepatitis C (duration of infection ≤18 months) enrolled in the ATAHC II (pegylated interferon-α2a + ribavirin) and DARE-C I (pegylated interferon-α2a, ribavirin and telaprevir) studies were included for analysis. Treatment duration was response-guided (ATAHC II: 8, 16, 24 or 48 weeks DARE-C I: 8, 12 or 24 weeks) and dependent on time to first undetectable HCV RNA using Roche Taqman HCV RNA testing. The primary efficacy end point was sustained virological response at 12 weeks (SVR12) by intention-to-treat. Logistic regression analyses were used to identify predictors of SVR. A total of 82 participants (62% HIV-positive) were enrolled in ATAHC II (treated, n=52) and 14 (79% HIV-positive) in DARE-C I. The predominant modes of HCV acquisition were injecting drug use (ATAHC II 55%, DARE-C I 36%) and sexual intercourse with a partner of the same sex (ATAHC II 39%, DARE-C I 64%). SVR12 was 71% in both ATAHC II (37/52) and DARE-C I (10/14) with 56% in ATAHC II receiving shortened therapy (8 or 16 weeks). SVR was associated with a rapid virological response (odds ratio 10.80 P=0.001). The majority of participants were able to receive short duration response-guided therapy with pegylated interferon-α2a and ribavirin. Response-guided therapy for recent hepatitis C infection could be considered in the absence of available interferon-free therapies. ClinicalTrials.gov registry (ATAHC II: NCT01336010 DARE-C I: NCT01743521).
Publisher: Wiley
Date: 26-11-2019
DOI: 10.1111/HIV.12689
Abstract: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional s le of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2% stroke, 7.5 versus 4.2% thrombosis, 10.5 versus 4.2% and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99 P = 0.03] and thrombosis (aOR 2.87 P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.
Publisher: Wiley
Date: 19-05-2014
DOI: 10.1111/HIV.12162
Abstract: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.
Publisher: Wiley
Date: 07-08-2011
No related grants have been discovered for Kathy Petoumenos.